Pharmacological doses of gonadrotropin releasing hormone (GnRH) and its agonists have been shown to inhibit female reproductive functions, such as ovarian steroidogenesis, ovulation, implantation, pregnancy and ovarian-dependent mammary tumorigenesis. Likewise, treating male rats with pharmacological doses of GnRH and its agonists results in a decrease in testicular steroidogenesis, a loss of testicular LH and prolactin receptors as well as a decrease in the weights of the testes, seminal vesicles and prostate. The mechanisms by which GnRH inhibits reproductive functions are unknown. We recently demonstrated that GnRH and GnRH agonists exert a direct action on the ovarian granulosa cells and the testicular Leydig cells. The inhibitory effect of GnRH on the granulosa cells was blocked by a GnRH antagonist. We propose here to extend this work by studying the direct effect of a wide variety of GnRH agonists and antagonists on female and male reproductive functions. We will study the effects of GnRH agonists and antagonists on steroidogenesis and LH, FSH, and prolactin receptor content in rat granulosa cells in vitro. We will also study the effect of GnRH and GnRH-like peptides on estrogen receptor content, protein and DNA synthesis, cyclic AMP formation and morphology of ovarian cells. Parallel studies will be performed in vivo in hypophysectomized female rats. Furthermore, similar studies on the regulation of Leydig cell functions by GnRH agonists and antagonists will be performed in hypophysectomized male rats, including testicular steroidogenesis, LH, FSH and prolactin receptor content and morphology. Finally, we will attempt to characterize specific GnRH binding sites in the granulosa and Leydig cells and to correlate receptor changes with functional studies. This proposed work on the effects of GnRH on gonadal functions will provide new information on our understanding of the extrapituitary site and mechanism of action of GnRH and allow for the future use of GnRH and its analogs as fertility and contraceptive agents.